GE Healthcare (Waukesha, Wisconsin) and Volcano (Rancho Cordova, California) last month reported what they are calling a “significant” development collaboration to bring an “industry-first” imaging capability to cardiac catheterization labs around the world. The companies will cooperate in developing a digital cardiovascular imaging system with integrated intravascular ultrasound imaging (IVUS) capabilities, the companies said.

Bradley Fox, business manager for the Interventional, Cardiology and Surgery business at GE Healthcare, in an e-mail response to questions from Cardiovascular Device Update, said that project resulted from exploratory discussion in 2004, “exchanging views on the marketplace and directions we were headed ... We found that we have a very similar view of where interventional cardiology is heading and that we both felt strongly that integration within the cath lab would be a major factor in both improving workflow and in enabling and optimizing new procedures.”

The integration of GE’s Innova all-digital X-ray cath lab system with Volcano’s new PC-based IVUS platform focuses on providing a precise view of coronary and peripheral vessel morphology for the interventional cardiologist. That capability will assist in determining the extent of cardiovascular disease to guide therapeutic procedures, such as stent placement, by determining the exact lesion length and stent length. “Our integration will be based on Volcano’s S5 device,” introduced at the recent Transcatheter Cardiovascular Therapeutics meeting in Washington, Fox said. The imaging device produced, he said, will be co-developed by Volcano’s team in Rancho Cordova and GE Healthcare’s cardiovascular X-ray team in Buc, France. Fox predicted that the integrated product will be available in 2Q06.

Fox said that a decision not to use IVUS “is heavily influenced by the workflow impact of having to wheel in and set up the IVUS system. The displays and data management are also not integrated.” By contrast, combining of technologies “allows the use of IVUS to be integrated into the workflow [to] simply select and plug in an IVUS catheter – the system will always be there, controlled from tableside with display integrated in the overhead monitors.”

William Wijns, MD, co-director of the Cardiovascular Centre (Aalst, Belgium), elaborated on the need for integration: “When you have a catheterized patient on the table, often in the midst of an acute syndrome, you need your diagnostic and therapeutic tools at the ready ... Many times it is just not an option to ask the staff to roll in the IVUS, turn it on and wait for the system to boot up. We have been asking for this advance from the IVUS companies for some time now.”

Scott Huennekens, president and CEO of Volcano, said in a statement, “We have a shared philosophy with GE [that] success in the marketplace is founded on providing solutions that are both state-of-the-art and simple to use.” He said the goal of the collaboration is not “technology for technology’s sake,” but rather “meeting the clinical needs of our customers in a way that also simplifies their lives and makes their own cath lab operations more efficient and more cost-effective – all while allowing the physician to improve patient care.”

Volcano says that its latest PC-based IVUS platform “dramatically reduces the size, weight and noise of the IVUS console, allowing the unit to be easily attached to the patient table, in the control room or in other areas outside of the daily traffic pattern of the cath lab.”

With more than 1,200 Innova all-digital X-ray systems installed worldwide, the companies say there is a clear market need for this type of integrated system.

GE also will collaborate with Volcano to provide cath lab design, installation and field repair/service of this new system. Current GE cath lab customers can modify existing cath lab rooms with the new integrated IVUS system. “The GE Innova systems and the Volcano S5 system have both received 510(k) clearance from the FDA,” Fox said in his e-mail. “We are evaluating what additional regulatory actions will be required for the integrated product.” After receiving U.S. and international clearances, the system will be co-marketed by the GE and Volcano organizations.

Volcano also reported that it had reached an agreement with Paieon (New York) to jointly develop products allowing in-the-cath-lab combination of X-ray angiography (in both 2-D and 3-D views) with intravascular ultrasound in the cath lab.

The Volcano/Paieon system is expected to allow physicians and their staff to quickly assess regions of the coronary tree and simultaneously visualize both the patency of the arterial lumen and the presence, quantity and type of coronary atherosclerotic plaques.

CoAxia seeks to widen stroke treatment window

Three hours is the window of time in which a stroke patient should be treated following the onset of an ischemic stroke. The best medical therapy includes such clot-busting drugs as Genentech’s (South San Francisco, California) tissue plasminogen activator (tPA). Now, CoAxia (Maple Grove, Minnesota) believes it has moved closer to pushing this window wider – to perhaps as long as 10 hours or more – with enrollment of the first patient in its multi-center trial evaluating the safety and efficacy of its cerebral perfusion augmentation therapy for ischemic stroke at Central DuPage Hospital (Winfield, Illinois).

Harish Shownkeen, MD, director of endovascular surgical neuroradiology at Central DuPage Hospital, in DuPage County, west of Chicago, treated the patient with the NeuroFlo catheter about 8-1/2 hours after symptoms were first reported. “This patient had no proven acute treatment options, due to the relatively long time from the onset of symptoms to treatment,” said Shownkeen. “The NeuroFlo catheter was deployed easily and treatment occurred with no issues.”

The CoAxia Safety and Efficacy of NeuroFlo Treatment for Ischemic Stroke (SENTIS) trial is an ambitious FDA-approved, randomized evaluation of NeuroFlo that will be enrolling about 400 patients at more than 40 sites in the U.S. and Canada. Patients will be treated up to 10 hours after stroke onset and be evaluated neurologically at 90 days. If successful, NeuroFlo could become an important treatment option for the many thousands of patients that arrive at hospitals beyond the time limit for delivery of present treatments. “What we do is kind of globally increase the blood flow in your whole brain,” said Rick Schallhorn, vice president of marketing and business development for CoAxia. “Theoretically, this thing should work as long as there’s tissue that can still be salvaged.”

He told Cardiovascualr Device Update that essentially the NeuroFlo “reroutes the flow of blood around these clots and we can bathe the periphery of the stroke.” He said this will help to limit the size and damage of a stroke. He said it is uncertain whether the device would be used in conjunction with best medical therapy in the long run. However, during the company’s clinical trial, he said, “We are not using it in conjunction with these other agents; it’s a stand-alone device.” And he said the reason why most other therapies aren’t used after a three- to five-hour window is because there’s a substantial risk of hemorrhaging associated with trying to remove a clot after that timeframe.

The idea which led to the formation of CoAxia in 1999 was generated from observations made by company founder Denise Barbut, MD, on patients undergoing coronary bypass surgery at Cornell University (Ithaca, New York), where she was a professor of neurology and in charge of stroke research. He observed that changes in systemic flow rate were paralleled by changes in cerebral blood flow, while changes in blood pressure had little effect on cerebral blood flow.

While the relation between blood pressure and cerebral blood flow was in keeping with cerebral autoregulation (which is the body’s ability to maintain steady cerebral blood flow regardless of fluctuations in blood pressure) the changes seen during fluctuations of flow rate at constant pressure were not.

“[Autoregulation] works against you potentially when you’re having a stroke because you can’t get enough blood pushed up [to the brain],” said Schallhorn. He said Barbut’s observation led her down a path to thinking there were ways to get more blood flow into the brain. The idea that ultimately evolved was using the bodies’ own pump, the heart, and creating additional vascular resistance in the lower body via the descending aorta, in order to direct more flow to the brain.

The tricky part, Schallhorn said, was finding a way to divert blood flow without changing systemic blood pressure. The NeuroFlo was developed as the solution to that problem. It is a catheter that is inserted in the femoral artery and advanced to the abdominal aorta, where its dual-balloon design provides the therapy.

One balloon is positioned above the renal arteries and the other below the renal arteries. This positioning, the company says, optimizes hemodynamic changes associated with device deployment. “The two balloons are inflated, not enough to cause a complete occlusion but enough to cause a significant diversion of flow,” Schallhorn said. After the catheter has been deployed for about 45 minutes, it is withdrawn, leaving the new pathway open around a clot.

One thing still uncertain is how long this new pathway will remain open, and Schallhorn acknowledged that is an unknown the company is attempting to address with this clinical trial

The company won a humanitarian device exemption from the FDA in April for use of the NeuroFlo in the treatment of cerebral ischemia in acute vasospasm, making it the first interventional device approved for use as a treatment for patients with cerebral vasospasm following repair of an aneurysmal subarachnoid hemorrhage. Vasospasm causes a reduction of cerebral blood flow, producing effects similar to those of strokes, and may cause permanent neurological disability or death.

The HDE approval by the FDA allows treatment of up to 4,000 patients per year. Schallhorn said the company recognizes that the stroke market – at more than 700,000 a year in the U.S. alone – would be a huge boost for CoAxia. “There’s no therapy at the moment that has been proven out many hours after stroke, that’s our big opportunity,” he said.

Schallhorn said he believes the current funds should get the company “well into execution of this trial.” However, he noted that with a possible two years needed to complete enrollment, the company will almost certainly need to raise another round in the future to finish the trial

FDA eyes suspension of Taxus stent use

The FDA last month said it was investigating why a Michigan hospital temporarily stopped using Boston Scientific’s (Natick, Massachusetts) Taxus drug-eluting coronary stents. The investigation was first reported by the Wall Street Journal which said that William Beaumont Hospital (Royal Oak, Michigan), suspended use of the devices in late September and early October after two patients suffered arterial injuries when the wires and balloons used to thread them into the body resisted removal. While the stents were put back into use without further problem, the incident led to a dispute in which a doctor from the hospital sent an e-mail to the FDA, questioning the stent’s safety, and said the company had mischaracterized the matter’s resolution.

In an Oct. 25 e-mail to Donna Lochner, the FDA’s deputy director of cardiovascular devices, Beaumont cardiologist James Goldstein said he was “surprised and disconcerted” to have heard from her at a recent cardiology meeting that following Beaumont’s reinstatement of the Taxus stent that that the company had told the agency that the issue of the hospital was solved. “This is not anywhere close to truth or reality,” Goldstein wrote. “We are very concerned that the withdrawal problems with the Taxus have not been solved,” he said. Lochner wrote back to Goldstein, assuring him that the FDA did not consider the situation to be a “closed matter.”

Boston Scientific spokesman Paul Donovan said in a statement that the FDA and the administration of Beaumont Hospital were satisfied with the way the company has addressed the complaints. Any remaining dissatisfaction, he said, was “out of proportion to our experience.” Donovan also noted that in recent months, doctors’ complaints to the FDA over withdrawal difficulties with the Taxus product had been reduced to fewer than one case in 10,000. The hospital resumed use of the stent after Boston Scientific provided additional training, Donovan said.

In the past, some cardiologists have reported that the Taxus stent has a tendency to get stuck during installation, causing them to have to apply extra force during the procedure During the procedure, the stents are expanded into place by an inflatable balloon at the tip of the installation wires that are threaded into arteries. Once the stent is in place, the balloon is deflated and removed.

At Beaumont Hospital, three Taxus systems reportedly became stuck within a five-day period in September. In two patients, the struggle to free the balloon led to tears in the lining of their arteries, which had to be patched with a second stent. Additionally, in one of the patients, the balloon used to deploy the repair Taxus got stuck as well.

Boston Scientific, which currently commands more than 50% of the DES market, last year recalled more than 99,000 Taxus DES stents following reports of malfunctions. The company made manufacturing changes to address the problem, which it attributed to a welding flaw affecting some Taxus and Express2 stents. The company disclosed in a note sent to doctors in July 2004 that there had been 43 complaints about a failure of a balloon to deflate involving the 500,000 Taxus stents implanted up to that point, and 52 involving 600,000 Express2 stents. In that note, the company said it had received reports of one death and 18 serious injuries associated with balloon deflation for the Taxus, and two deaths and 25 serious injuries linked to the Express2.

The FDA said in July that it was working with the company to “identify possible causes and solutions to the problem,” after another WSJ article, citing FDA data, said that the deflation issue had caused three people to die and dozens more were injured during surgeries after last year’s recall and product fix.

According to a more recent analysis by an independent clinical research firm commissioned by Boston Scientific, the FDA received reports of Taxus withdrawal problems in 485 patients in the 30 months that ended in June. The reports included 79 serious injuries. During that same time period, the Boston Scientific analysis showed the FDA received reports of stent withdrawal problems in 28 patients who received the Cypher stent made by Johnson & Johnson’s (New Brunswick, New Jersey) Cordis (Miami Lakes, Florida) unit, with 15 of those involving serious injuries.

Ev3 scoops up MTI’s remaining shares

ev3 (Plymouth, Minnesota) last month said that one of its subsidiaries will acquire and be merged into Micro Therapeutics (MTI; Irvine, California), an endovascular medical device company focused on neurovascular disease and disorders. ev3, which already owns some 70.1% of MTI’s common stock through a wholly owned subsidiary, will acquire all of MTI’s shares that it does not already own in a tax-free transaction.

Under the agreement, MTI stockholders will receive 0.476289 of a share of ev3 common stock for each share of MTI common stock held. This exchange ratio represents a 4% increase in the number of ev3 shares to be issued to each MTI stockholder from the proposed exchange ratio reported in October in connection with ev3’s initial proposal.

ev3 would issue about 6.9 million new shares of its common stock to MTI public stockholders upon the closing of the transaction, bringing ev3’s total pro forma outstanding shares to roughly 56.1 million. In addition, ev3 would assume all of the outstanding options to purchase MTI common stock under that company’s stock option plans.

MTI makes minimally invasive medical devices for the diagnosis and treatment of vascular disease. The company is focused on catheter-based, or endovascular, technologies for the minimally invasive treatment of neurovascular disorders of the brain associated with stroke. MTI’s products include the NXT and Nexus lines of embolic coils, the Onyx liquid embolic and a range of access and delivery products that include micro delivery catheters, balloon catheters and guidewires.